Field of the Invention
The invention relates to an apparatus and a method for controlling the crystal growth of macromolecules, especially of biological macromolecules.
Description of the Related Art
A key task in the field of biochemistry and molecular biology is the atom-precise elucidation of three-dimensional structure of biomolecules, especially proteins. Most currently available structural models of proteins and other biomolecules in the resolution range of 0.25 nm and better were obtained using X-ray crystallography. A precondition for the application of this procedure is the presence of single crystals. The degree of internal order of the crystal determines significantly the quality of the data obtained and thus the precision of the elucidated structure.
Due to the large number of parameters that influence the crystallization of proteins (concentration of the material to be crystallized, the concentration of solvent, concentration of the precipitant, concentration further auxiliaries, changes in pH, changes in temperature, etc. . . . ) it is, to this day, hard to obtain reproducible results in crystallization.
From U.S. Pat. No. 4,919,899 an apparatus for the production of protein crystals is known. The method employed is known as the “hanging drop” method, wherein the concentration of the components of the droplets is controlled via evaporation or addition of the solvent. An automated optimization of the crystallization conditions is envisioned.
The dynamic control of crystal growth for proteins is also known from US2001006807 A1. Here, the concentration of the solvent is controlled via the temperature and the gas stream.
All known methods for reproducible and automated crystallization have in common that, by influencing a parameter, a predetermined or fixed path in the phase diagram is followed.
Especially water-insoluble proteins, such as membrane proteins which are of particular interest for drug activity investigation, are not available by reproducible and automated crystal growth.